During the last decades a dramatic increase in bacterial strains multiresistant to antibiotics has been reported. This increase has led to the occurrence of incurable bacterial infections with a fatal outcome, and a particularly serious problem in connection with hospital-acquired infections. The emergence of antibiotic resistance is a result of the overwhelming use of antibiotics in human and veterinary medicine. Furthermore, the incidence of allergy towards the presently most effective antimicrobials further complicates the treatment of bacterial infections.
It is generally believed that if the bacterial membrane could only be permeabilized, the effect of antibiotics would be enhanced. A great deal of effort has gone into attempts to permeabilize the Gram negative outer membrane to antibiotics in the hope that some permeabilizers may prove clinically useful. Several polycations have been shown to permeabilize the outer membrane, presumably by binding to lipopolysaccharide (LPS). Among the polycation permeabilizers are polymixin B and its derivatives (Vaara, M., and Vaara, T., 1983), including deacylpolymixin B and polymixin B nonapeptide (Viljanen, P. H. et al., 1991). Other polycationic permeabilizers include bactericidal/permeability-increasing protein, protamine, and various polycationic peptides including lysine polymers, defensins, cecropins, magainins, and mellitin. Chelators, such as ethylenediaminetetraacetate (EDTA), nitrilotriacetate, and sodium hexametaphosphate have proved to be effective outer membrane permeabilizers. Chelators presumably permeabilize by removing calcium and magnesium ions from LPS, resulting in release of much of the LPS from the outer membrane and consequent outer membrane destabilisation.